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Dan Hoft, M.D., Ph.D., Lab

professor Daniel Hoft supervising student on a presentation creation
 

Dr. Daniel Hoft, M.D., Ph.D., focuses on developing vaccines against mucosally transmitted, intracellular pathogens in both animal models and humans. His lab was first to report that CD4+ Th1 and not Th2 cells provide mucosal and systemic protection, indicating that coordinated mucosal/systemic immunity is achievable. His lab reported the first evidence that CD4+ Th17 cells provide potent helper effects for induction of protective CD8+ T cells, implicating Th17 cells as important targets for vaccines against intracellular pathogens and cancer. His group pioneered use of immunoinformatics to develop T cell-targeting, “universal” vaccines to protect all human populations against future influenza pandemics. In addition to contributions in pre-clinical vaccinology, Hoft has conducted human trials with the goal of improving tuberculosis (TB) vaccines. Although BCG vaccines are available, protection is limited and better vaccines are urgently needed. Hoft’s clinical trials have tested whether mucosal, booster and/or novel recombinant vaccinations can enhance TB immunity. His lab was first to demonstrate that human γ9δ2 T cells can provide TB protective memory responses, a paradigm shift providing new approaches for TB vaccination. Furthermore, Hoft’s lab has identified new TB antigens that induce protective γ9δ2 T cells, now being studied in nonhuman primates. Hoft serves as Director of the Saint Louis University Center for Vaccine Development, which has received millions in NIH funding through contracts and awards, including a Vaccine & Treatment Evaluation Unit cooperative grant placing SLU among an elite group of top academic centers conducting phase I through III trials of novel vaccines for global protection against future pandemic challenges. Since the COVID-19 pandemic began, Hoft has led urgent vaccine trials, which continue to be ongoing, and is conducting new research focused on the development of universal pandemic coronavirus vaccines.

student grabbing samples out of storage safe
 

Valerio Rasi is an M.D./Ph.D. student (G5) originally from Italy. After graduating summa cum laude from the University of Florida with a degree in biochemistry, he joined the Saint Louis University M.D./Ph.D. program in 2015. He is currently finishing his Ph.D. in Molecular Microbiology and Immunology under the mentorship of Daniel Hoft, M.D., Ph.D. Throughout his time at SLU, Rasi obtained the prestigious pre-doctoral (F30) fellowship from the National Institute of Health, which is currently funding his Ph.D. and the remaining portion of his M.D. His research focuses on understanding how a protein secreted by γ9δ2 T cells, Granzyme A, inhibits the intracellular replication of mycobacterium tuberculosis within human macrophages. Outside of research, he enjoys traveling, swimming and cooking.

Daniel Hawiger, M.D., Ph.D., Lab

Dr. Hawiger's Lab

 Daniel Hawiger, M.D., Ph.D. and students Andrew Jones and Jessica Bourque.

Dendritic cells (DCs) have crucial roles in priming effector T cells but DCs also have critical tolerogenic functions in the peripheral immune system, extending the maintenance of immune homeostasis and blocking autoimmune responses. However, broad tolerogenic functions of DCs including induction of peripheral regulatory T cells (pTreg cells) could hamper protective immune responses against some pathogens and tumors, whereas an inadvertent activation of autoregressive T cells in the presence of pro-inflammatory stimuli could lead to autoimmunity. Therefore the maintenance of immune homeostasis by DCs requires specific mechanisms that actively adjust T cell functions to promote tolerance while preserving an overall high plasticity of the immune responses.

(DCs with specialized tolerogenic functions are represented here as red flowers attracting naïve T cells depicted as green bees that can acquire regulatory functions, symbolized as purple halos. Trends in Immunology, 2017, Nov;38(11):793-804). 

To clarify the mechanisms by which DCs govern T cell tolerance in the context of autoimmune disorders such as multiple sclerosis (MS) but also other immune responses, studies in my laboratory are focused on the roles of specialized subsets of DCs and their specific functions in tolerance as well as the relevant molecular mechanisms induced by such DCs in T cells. Our work has elucidated the functions of specific immunomodulatory pathways, cell signaling regulators and transcription factors that establish tolerogenic outcomes of the interactions between T cells and DCs. 

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